Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.
Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.
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DOI：
10.1097/j.pain.0000000000000953
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发表时间：
2017-09
期刊：
影响因子：
7.4
通讯作者：
Baccei ML
中科院分区：
文献类型：
--
作者：
Schappacher KA;Styczynski L;Baccei ML
长春新碱（VNC）通常用于治疗儿童癌症，包括最普遍的儿童恶性肿瘤，急性淋巴细胞白血病。虽然临床证据表明，VNC引起儿童周围神经病变，但儿童化疗方案影响终生疼痛敏感性的程度仍不清楚，部分原因是缺乏早期化疗诱导的神经性疼痛的既定动物模型。因此，本研究探讨了出生后第11天至21天期间VNC暴露对发育中的大鼠机械和热痛敏感性的影响。低剂量的VNC（15或30 μg/kg）未能改变任何年龄的伤害性戒断反射。同时，高剂量VNC （60 μg/kg）在P26开始引起两性机械超敏反应，持续到成年，包括静态和动态机械异常性疼痛。高剂量VNC不影响后肢对毒热和毒冷的戒断潜伏期，提示新生儿VNC对机械疼痛敏感性的选择性作用。在VNC治疗后，粗大和精细运动功能恢复正常，尽管体重增加略有减少。VNC方案还通过P33显著降低了后爪皮肤表皮内神经纤维（IENF）密度。总的来说，目前的结果表明，在出生后早期，高剂量的VNC有选择性地引起了青春期缓慢出现的机械超敏反应，进一步证明了早期生活中异常的感觉输入可能会对疼痛处理产生长期的影响。
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, Acute Lymphoblastic Leukemia. While clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part due to the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, the present study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared to vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood, and included both static and dynamic mechanical allodynia. Hindpaw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber (IENF) density in the hindpaw skin by P33. Overall, the present results demonstrate that high dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.
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影响因子：
64.5
作者：
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q
通讯作者：
Ma Q
影响因子：
3
作者：
Boyette-Davis, Jessica A.;Cata, Juan P.;Driver, Larry C.;Novy, Diane M.;Bruel, Brian M.;Mooring, Deidre L.;Wendelschafer-Crabb, Gwen;Kennedy, William R.;Dougherty, Patrick M.
通讯作者：
Dougherty, Patrick M.
DOI：
10.1111/j.1460-9568.2011.07652.x
发表时间：
2011-05
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Bennett GJ;Liu GK;Xiao WH;Jin HW;Siau C
通讯作者：
Siau C
影响因子：
13.9
作者：
Costigan M;Scholz J;Woolf CJ
通讯作者：
Woolf CJ
DOI：
10.1073/pnas.96.14.7719
发表时间：
1999-07-06
影响因子：
11.1
作者：
Fitzgerald, M;Jennings, E
通讯作者：
Jennings, E